CHRM3 Membrane Protein Introduction

Introduction of CHRM3

CHRM3, encoded by CHRM3 gene, is a member of G protein-coupled receptors family which has seven distinctive transmembrane domains. It is one of five subtypes of muscarinic receptors (CHRM1-5), selectively expressed in various human tissues, including brain, salivary gland, and 12 other tissues. Researchers have found that muscarinic receptors are the potential therapeutic targets for a variety of pathological conditions, especially in neurodegenerative disorders.

Function of CHRM3 Membrane Protein

CHRM3 is a receptor for acetylcholine. The binding of acetylcholine and these receptors induces diversified functions including cellular cell signaling transduction. Activities of the receptors can upregulate phospholipase C and inositol trisphosphate, thereby launching a signaling, controlling multiple body metabolisms. The expression of CHRM3 on pancreatic β-cells and in the brain can regulate insulin homeostasis via vagal innervation of the gastrointestinal tract. It plays a critical regulator of glucose homeostasis by modulating insulin secretion and is involved in the pathological process of type 2 diabetes mellitus. Moreover, CHRM3 is also located in many other glands, both endocrine and exocrine gland and controls the secretion of various glands. Recently, the findings reveal that CHRM3 is associated with the pathological process of kinds of cancer, such as colon neoplasia, bladder cancer, and gastric cancer. Moreover, CHRM3 is a well-characterized drug target for the treatment of asthma and obstructive lung disease.

Fig.1 Structure of CHRM3.

Application of CHRM3 Membrane Protein in Literature

1. Yu X., et al. Autoantibodies against muscarinic acetylcholine receptor M3 in Sjogren's syndrome and corresponding mouse models. Frontiers in bioscience (Landmark edition). 2018, 23: 2053-2064. PubMed ID: 29772545
   
   

   CHRM3 is a receptor on exocrine gland cells involved in fluid secretion. In this review, the authors summarize clinical data and findings from experimental disease to propose a hypothetic model for the role of autoantibodies against M3R in the pathogenesis of Sjögren's syndrome.

2. Felton J., et al. Targeting M3 muscarinic receptors for colon cancer therapy. Curr Mol Pharmacol. 2018, 11(3): 184-190. PubMed ID: 29357811
   
   

   The article shows that M3R, post-M3R signaling, or MMP1 can be regarded as the potential targets to prevent or reverse metastatic spread of colon cancer cells.

3. Wain L V., et al. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nature Genetics. 2017, 49(3): 416. PubMed ID: 28166213
   
   

   The authors provide the evidence regarding genetic variant (genes in the inositol phosphate metabolism pathway and CHRM3) associated with chronic obstructive pulmonary disease and asthma (COPD) and identify the new loci and potential drug targets.

4. Chen X., et al. Overexpression of M3 muscarinic receptor suppressed adverse electrical remodeling in hypertrophic myocardium via increasing repolarizing K⁺ currents. Cellular Physiology & Biochemistry. 2017, 43(3): 915-925. PubMed ID: 28957802
   
   

   The article shows that CHRM3 overexpression increase potassium currents, promote repolarization, thereby inhibiting adverse electrical remodeling in cardiac hypertrophy.

5. Wang C T., et al. The functional haplotypes of CHRM3 modulate mRNA expression and associate with bladder cancer among a Chinese Han population in Kaohsiung city. BioMed Research International. 2016, 2016(1): 1-10. PubMed ID: 28053981
   
   

   The study is the first to reveal the CHRM3 genetic association with bladder cancer. Results implicate that five haplotypes (GTTAT, ATTGT, GCTAC, ACTAC, and ACCAC) are significantly associated with the low CHRM3 mRNA level. And they are involved in the increased susceptibility of bladder cancer in Kaohsiung city.

CHRM3 Preparation Options

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